Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2

Nature
G F GaoB K Jakobsen

Abstract

The dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of cytotoxic T cells in the thymus. The homodimer CD8alpha(alpha) or the heterodimer alpha beta stabilizes the interaction of the T-cell antigen receptor (TCR) with major histocompatibility complex (MHC) class I/peptide by binding to the class I molecule. Here we report the crystal structure at 2.7 A resolution of a complex between CD8alpha(alpha) and the human MHC molecule HLA-A2, which is associated with peptide. CD8alpha(alpha) binds one HLA-A2/peptide molecule, interfacing with the alpha2 and alpha3 domains of HLA-A2 and also contacting beta2-microglobulin. A flexible loop of the alpha3 domain (residues 223-229) is clamped between the complementarity-determining region (CDR)-like loops of the two CD8 subunits in the classic manner of an antibody-antigen interaction, precluding the binding of a second MHC molecule. The position of the alpha3 domain is different from that in uncomplexed HLA-A2, being most similar to that in the TCR/Tax/HLA-A2 complex, but no conformational change extends to the MHC/peptide surface presented for TCR recognition. Although these shifts in alpha3 may provide a synergistic modulation of affinity, the binding of CD8 to M...Continue Reading

References

Oct 15, 1979·Journal of Molecular Biology·D I StuartD K Stammers
May 21, 1992·Nature·C J WheelerJ R Parnes
Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Nov 3, 1988·Nature·A M NormentD R Littman
Jan 20, 1995·Science·T Clackson, J A Wells
Dec 1, 1994·Current Opinion in Structural Biology·I A Wilson, R L Stanfield
Jan 1, 1995·Annual Review of Immunology·D R Madden
Mar 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·P A GiblinP B Kavathas
Nov 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·E A Merritt, M E Murphy
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

❮ Previous
Next ❯

Citations

May 30, 1998·Protein Science : a Publication of the Protein Society·G F GaoB K Jakobsen
Jan 18, 2005·Immunogenetics·Paula P CardenasManuel A Patarroyo
Jan 5, 2011·Cancer Immunology, Immunotherapy : CII·Andrew ZlozaJosé A Guevara-Patiño
Aug 30, 2008·Immunologic Research·Edward J Collins, David S Riddle
Dec 5, 2009·Journal of Molecular Neuroscience : MN·Alexander O Tarakanov, Kjell G Fuxe
Jan 5, 2011·Protein & Cell·Yong ChenGeorge F Gao
Mar 20, 1999·Transplantation Proceedings·P F Halloran
Mar 1, 2008·Nature Reviews. Immunology·Werner Held, Roy A Mariuzza
Oct 11, 2008·Nature Reviews. Immunology·Nicholas R J Gascoigne
Mar 31, 1998·Scandinavian Journal of Immunology·J Klein, A Sato
Jul 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Zhiru Yang, Pamela J Bjorkman
Sep 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Shota EndoToshiyuki Takai
Jul 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Mitsunori ShiroishiKatsumi Maenaka
Aug 24, 2010·The Journal of Biological Chemistry·Zu T ShenLawrence J Stern
Jan 21, 2012·The Journal of Biological Chemistry·Ricardo A FernandesSimon J Davis
Jan 11, 2003·Biotechnology & Genetic Engineering Reviews·Anna P TretiakovaBradford A Jameson
Oct 9, 2013·The Journal of Experimental Medicine·Rangsima ReantragoonLars Kjer-Nielsen
Jun 22, 2012·Human Molecular Genetics·Paul J McLarenUNKNOWN International HIV Controllers Study
May 16, 2013·Current Opinion in Rheumatology·Barbara Uchanska-ZieglerPeter Schmieder
Mar 3, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·David K ColeGeorge F Gao
Mar 3, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Tatyana SandalovaAdnane Achour
Sep 5, 2007·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Fang YuanBent K Jakobsen
Apr 13, 2010·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Lili ZongJianhua Zhang
Aug 9, 2011·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Nianzhi ZhangChun Xia
Oct 25, 2000·Protein Science : a Publication of the Protein Society·O Schueler-FurmanH Margalit
Jan 22, 2005·Immunology and Cell Biology·Nazzareno Dimasi, Roberto Biassoni
Aug 13, 1998·Immunological Reviews·I D Campbell
Aug 13, 1998·Immunological Reviews·E Y JonesD I Stuart
Aug 13, 1998·Immunological Reviews·C A O'Callaghan, J I Bell
Aug 13, 1998·Immunological Reviews·E J Collins, J A Frelinger
Aug 13, 1998·Immunological Reviews·G MazzaB Malissen
Aug 13, 1998·Immunological Reviews·Z Weng, C DeLisi

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.